title: Serum levels of biomarkers of bone and cartilage destruction and new bone formation in different cohorts of patients with axial spondyloarthritis with and without tumor necrosis factor-alpha blocker treatment.
abstract: BACKGROUND
  Recent data about radiographic progression during treatment with tumor necrosis factor-alpha (TNF-alpha) blocker agents in patients with ankylosing spondylitis (AS) have prompted an intensive discussion about the link between inflammation/bone destruction and new bone formation and the order of events. Therefore, we analysed parameters of cartilage degradation, neoangiogenesis, and new bone formation in different cohorts of patients with axial spondyloarthritis with and without treatment with TNF-alpha blocker agents.
  
  
  METHODS
  TNF-alpha blocker-naïve AS patients were investigated for serum levels of metalloproteinase-3 (MMP-3) (n = 71), vasoendothelial growth factor (VEGF) (n = 50), and bone-specific alkaline phosphatase (BALP) (n = 71) at baseline and after 1 and 2 years. This was compared with 34 adalimumab-treated patients with axial spondyloarthritis (22 AS and 12 non-radiographic axial spondyloarthritis patients) before and after 36 to 52 weeks of treatment.
  
  
  RESULTS
  There were no significant changes in serum levels of MMP-3 (P > 0.05), VEGF (P > 0.05), and BALP (P > 0.05) in a large cohort of TNF-alpha blocker-naïve AS patients followed for 2 years. In contrast, adalimumab-treated spondyloarthritis (AS and non-radiographic axial spondyloarthritis) patients had a significant decrease of VEGF (P < 0.001) and MMP-3 (P = 0.022) after 36 to 52 weeks of therapy. Most interestingly, the level of BALP increased significantly after 36 to 52 weeks of therapy (P < 0.001). A decrease in MMP-3 serum levels correlated significantly to an increase of BALP (r = -0.398, P = 0.02). In the case of VEGF, there was a negative correlation without significance (r = -0.214, P > 0.05).
  
  
  CONCLUSIONS
  Rising levels of BALP and the negative correlation between MMP-3 and BALP in spondyloarthritis patients with TNF-alpha blocker treatment indicate that new bone formation in AS occurs if inflammation is successfully treated and might be part of a healing process.
authors.affiliation: Department of Gastroenterology, Infectiology and Rheumatology, Charité Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. heiner.appel@charite.de
authors.forename: Heiner
authors.initials: H
authors.lastname: Appel
authors.forename: Louise
authors.initials: L
authors.lastname: Janssen
authors.forename: Joachim
authors.initials: J
authors.lastname: Listing
authors.forename: René
authors.initials: R
authors.lastname: Heydrich
authors.forename: Martin
authors.initials: M
authors.lastname: Rudwaleit
authors.forename: Joachim
authors.initials: J
authors.lastname: Sieper
mesh_terms: D000068879:Adalimumab; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers / Q000097:blood*; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology; D002356:Cartilage / Q000187:drug effects / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood / Q000187:drug effects; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D000469:Alkaline Phosphatase; D019278:Matrix Metalloproteinase 3; D000068879:Adalimumab